Effect of Normalization of Fasting Glucose by Intensified Insulin Therapy on the Incidence of Restenosis After Peripheral Angioplasty in Patients With Type 2 Diabetes.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Reduction of restenosis after peripheral angioplasty
研究概览
简要总结
Primary objective of the study is to test whether an intensified insulin therapy incorporating the target of normal fasting glucose (<5.5 mmol/L) and glycated hemoglobin <6.5% is able to halve the incidence of angiographic restenosis at 6 months (expected rate 45%, to be reduced at 15%) after peripheral angioplasty compared with standard care to achieve a glycated hemoglobin <7.0% in patients with type 2 diabetes and limb ischemia.
Secondary objectives include the identification of markers associated with, and predictive of, restenosis and the investigation of the underlying pathophysiological background, with specific focus on the role of nitric oxide (NO), mechanisms of endothelial activation/apoptosis, inflammation and matrix remodeling risk profiles, candidate gene polymorphisms and endothelial progenitor cells evaluation.
Methodology: This is a randomized, open-label, clinical trial comparing two regimens of insulin therapy having as an outcome measure the incidence of angiographic restenosis at 6 months after peripheral angioplasty. Seventy consecutive patients with type 2 diabetes and peripheral arterial disease undergoing peripheral angiography and subsequent angioplastic procedure will be studied. Patients will be treated by intensive insulin therapy, based on three pre-prandial administrations of regular insulin or short acting insulin analogues combined with the long-acting insulin analogue glargine or standard care based on once-daily insulin and oral antidiabetics agents. Patients randomized to the intensive insulin therapy arm will be educated and followed up with daily measurements of fasting glucose and weekly phone contacts with the target of fasting glucose <5.5 mmol/L (99 mg/dl) to obtain glycated hemoglobin <6.5%. The control arm will be followed to achieve a target of glycated hemoglobin <7.0%. Life style recommendations, including diet and physical activity program, will be the same for the two arms. All patients will undergo three visits with physical examination and blood sampling, at baseline and at 2, 4 and 6 months after angioplasty. Moreover, patients on normal fasting glucose arm will be monitored by phone on weekly basis in order to test their adherence to therapeutic target.
详细描述
The principal objectives of this project are:
Objectives Primary Objectives
To determine the role of fasting normoglycemia achieved with long term (6 months) intensified insulin therapy in:
- Reduction of angiographic restenosis (> or=50%) after peripheral angioplasty
- Increase in the rate of primary clinical success at follow-up defined as continued relief of ischemic rest pain, reduction in severity of claudication with persistent hemodynamic success and/or symptomatic improvement of at least one category according to Rutherford criteria, healing of ulceration, and freedom from unplanned surgical amputation or bypass surgery
- Definition of the beneficial effect of normoglycemia in insulin mediated nitric oxide (NO) modulation of neointima formation through its action on inflammation and/or matrix remodelling Secondary Objectives
- To determine whether fasting normoglycemia achieved with intensified insulin therapy is able to reduce or avoid planned or unplanned major amputation as limb loss above the metatarsal level and minor amputation, as transmetatarsal amputation or removal of more distal parts of the lower extremity and/or the performance of less extensive amputation than initially intended through 6 months
- To evaluate the reduction of Major Adverse Cardiovascular Event (MACE) defined as the occurrence of death, or repeat target vessel revascularization
- To find new risk profiles of systematically detectable indices able to define the patients at the highest risk to develop restenosis
- To correlate angiographic and clinical indices of restenosis with endothelial activation/apoptosis, inflammation and matrix remodelling risk profiles
- To define the association of candidate genes variants and the degree of restenosis
- To understand the impact of fasting normoglycemia achieved with intensified insulin therapy on endothelial progenitor cells isolation and gene expression involved in the process of vascular repair and in the inhibition of neointimal hyperplasia
This is a randomized, open-label, clinical trial comparing two regimens of insulin therapy (intensified insulin therapy vs standard care) to determine if fasting normoglycemia achieved with intensified insulin therapy is able to reduce the incidence of angiographic restenosis at 6 months after peripheral angioplasty.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Both genders
- •Age between 30 and 75 years
- •Early type 2 diabetes, defined as FPG >7.0 mmol/l or a PPG of 11.1 mmol/l or greater or a previous diagnosis of diabetes
- •Treatments accepted
- •Diet without pharmacological treatment
- •One or more oral antidiabetic drug (OAD: sulfonylureas, biguanides, meglitinides) at half-maximum dose or greater
- •Once daily insulin and OAD
- •Angiographic documentation of infrapopliteal arterial disease (stenosis >70% or occlusion)
- •Critical limb ischemia (CLI) defined as
- •Persistent, recurring rest pain requiring analgesia and an ankle systolic pressure <50 mm Hg and/or toe systolic pressure <30 mm Hg or TcPO2 <30 mm Hg
- •Ulceration, gangrene, or nonhealing wounds of the foot with ankle systolic pressure <50 mm Hg or toe systolic pressure <30 mm Hg or TcPO2 <30 mm Hg
- •Fontaine stages III-IV and rutherford categories IV-VI
- •Lifestyle-limiting claudication defined as Rutherford category II to III associated with jeopardized single vessel runoff or complete trifurcation vessel occlusion.
- •Subject able to provide a signed and dated written informed consent
排除标准
- •Type 1 diabetes, defined as positivity for GAD antibodies measured by radiobinding assay
- •Unwilling to inject insulin or to perform a correct self monitoring of blood glucose
- •Acute limb ischemia
- •Buerger disease
- •Severe contrast allergy
- •Hypersensitivity to aspirin and/or clopidogrel
- •Systemic coagulopathy contraindicating antiaggregation therapy
- •Hypercoagulation disorder
- •Serum creatinine>2.0 mg/dl at screening
- •Active liver disease, or ALT or AST >2.5 times upper limit of normal at screening
- •Chronic or recurrent treatment with systemic corticosteroids
- •Malignant diseases
- •Psychiatric diseases which make participation impossible
- •Alcohol abuse
研究组 & 干预措施
long-acting insulin plus analogues
three administrations of regular insulin or short acting insulin analogues before meals combined with long-acting insulin analogue glargine in the evening.
干预措施: Insulin glargine plus insulin analogues (Drug)
long-acting insulin and oral agents
treatment will be once-daily long-acting insulin and oral antidiabetic agents
干预措施: Insulin glargine plus insulin analogues (Drug)
结局指标
主要结局
Reduction of restenosis after peripheral angioplasty
时间窗: 6 months, average up to 30 weeks
Primary objective of the study is to test whether an intensified insulin therapy incorporating the target of normal fasting glucose (\<5.5 mmol/L) and glycated hemoglobin \<6.5% is able to halve the incidence of angiographic restenosis at 6 months (expected rate 45%, to be reduced at 15%) after peripheral angioplasty compared with standard care to achieve a glycated hemoglobin \<7.0% in patients with type 2 diabetes and limb ischemia.
次要结局
- Identification of new peripheral markers predictive of restenosis(6 months, average up to 30 weeks)